Granule cell dispersion is restricted across transverse boundaries in mouse chimeras

The granular layer of the developing and adult cerebellum is marked by the presence of several transverse boundaries, revealed in gene expression patt erns or as a consequence of genetic mutations, It is unclear whether these boundaries represent fundamental differences between granule cell populatio ns or if they are a secondary response to regional differences in the under lying Purkinje cells. One possibility is that boundaries mark different spa tial domains of granule cells in a lineage-dependent fashion. To test this hypothesis, we have analysed a series of murine embryonic stem cell chimera s marked by the constitutive expression of beta-galactosidase in donor gran ule cells. The chimeras show a consistent spatial restriction boundary, loc ated in the granular layer of lobule VI in the vermis and extending lateral ly into crus I of the hemispheres. A second boundary was found separating l obules IX and X in the vermis. No correlation was found between the genotyp es of molecular layer interneurons and the underlying granule cells, sugges ting that they arise independently. No transverse boundaries were observed for the molecular layer interneurons, consistent with the hypothesis that t hey are not generated from precursors in the external granular layer. These results indicate that the granular layer of the cerebellum comprises cellu lar domains with different histories separated by consistent spatial restri ction boundaries.